The spontaneously diabetic "BB" Wistar rat has been shown to have a syndrome akin to that of human insulin-dependent diabetics, telescoped into a short time span. Pancreatic beta cells are destroyed by an immune-related process in genetically susceptible rats, resulting in a fatal insulin-deficient, ketotic, hyperglucagonemic syndrome if untreated. This research is aimed at the elucidation of etiologic mechanisms in the beta-cell destruction with a view to ultimate prevention. The ongoing research is aimed at completion of a study of glucagon secretion using that in situ pancreas preparation in diabetic rats. The study of insulin secretion (in vivo and in the in situ pancreas preparation) in rats with impaired glucose tolerance will also be assembled for publication. The major effort will be in confirmation of our pilot results on passive transfer of insulitis from newly diagnosed diabetic rats to nude mice, as well as to BB rat recipients. In vitro studies of cytotoxicity of lymphocytes from such rats on cultured normal BB rat beta cells will be performed, and the mechanism of such an effect evaluated.